Absorption Studies of Albendazole and Some Physicochemical Properties of the Drug and Its Metabolite Albendazole Sulphoxide

Jung, Hyejin; Medina, Latorre; García, López; Fuentes, Inés; Moreno‐Esparza, Rafael

doi:10.1111/j.2042-7158.1998.tb03303.x

Cited by 118 publications

(85 citation statements)

References 13 publications

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“…1 The poor intestinal absorption of albendazole, which can be enhanced by a fatty meal, is a major factor that contributes to this problem. 2,3 After absorption, the drug is rapidly converted by the liver and probably also by mucosal cells into the active metabolite ABZSX, a mixture of R(+) and S(−) enantiomers. Formation of R(+)ABZSX is catalyzed by microsomal flavin mono-oxidase (FMO) and of S(−)ABZSX by cytochrome P450 enzymes (CYP3A).…”

Section: Introductionmentioning

confidence: 99%

Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.

Nagy¹,

Schipper²,

Koopmans³

et al. 2002

Am J Trop Med Hyg

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Abstract. The assumed metabolic breakdown of albendazole by mucosal CYP3A4 enzymes was studied by coadministering albendazole (10 mg/kg) with grapefruit juice. Concentrations of albendazole sulfoxide (ABZSX), the active metabolite of albendazole, were compared with those after albendazole was administered with water, a fatty meal, or grapefruit juice plus cimetidine (10 mg/kg). In comparison to water, maximum ABZSX concentration (C max ) was enhanced 6.5-fold by a fatty meal (from 0.24 ± 0.09 mg/l to 1.55 ± 0.30 mg/l; mean ± SD; P < 0.001) and 3.2-fold by grapefruit juice (from 0.24 ± 0.09 mg/l to 0.76 ± 0.37 mg/L; P ‫ס‬ 0.031). When grapefruit juice was combined with cimetidine, C max was significantly lower than with grapefruit juice alone (0.41 ± 0.29 mg/l and 0.76 ± 0.37 mg/l, respectively; P ‫ס‬ 0.022). The area under the concentration-time curve from 0 to infinity (AUC 0-⍀ ) followed a comparable pattern. Half-life (T 1/2 ) was 8.8 ± 4.2 hr and 8.2 ± 4.3 hr after administration with water or a fatty meal (P ‫ס‬ 1.000). Grapefruit juice shortened T 1/2 by 46% (P ‫ס‬ 0.026). We hypothesize that albendazole is metabolized by CYP3A4 enzymes in the intestinal mucosa. This process can be inhibited by grapefruit juice. Cimetidine decreased albendazole bioavailability.

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Section: Introductionmentioning

confidence: 99%

Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.

Nagy¹,

Schipper²,

Koopmans³

et al. 2002

Am J Trop Med Hyg

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“…ABZ belongs to type II biopharmaceutical classification system, with low aqueous solubility (0.01 mg/ml in water at 25°C) and high permeability (25).…”

Section: Introductionmentioning

confidence: 99%

Improved Albendazole Dissolution Rate in Pluronic 188 Solid Dispersions

et al. 2010

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Abstract. Solids dispersions (SDs) have been proposed as an alternative to improve the dissolution rate of low solubility drugs. SDs containing albendazole (ABZ; 5, 10, 25, and 50% w/w) and Pluronic 188 (P 188) as hydrophilic carrier were formulated. The obtained SDs were assessed in comparison to physical mixtures (PMs). Drug-polymer interactions in solid state were investigated using Fouriertransform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analysis. No chemical interaction was found between ABZ and poloxamer. The dissolution profiles indicated that ABZ incorporated in SDs and PMs was rapidly released, reaching rapidly the steady state. Increased dissolution rates are usually observed at the highest polymer proportions. However, an opposite effect for SDs as well as for PMs was observed in the assays described here. The systems with the lowest P 188 percentages (SD4, SD3; PM4, PM3) tended to be more effective in increasing the ABZ dissolution rate. Such a result can be attributed to the fact that concentrated aqueous solutions of Poloxamer may form thermo-reversible gels. The physical-mechanical properties indicated that SDs possess improved flow and compacting properties compared to PMs. Thus, ABZ SDs would be more convenient for solid dosage form design and manufacture.

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“…In the present investigation, the impact of excipients and of free base vs. salt on concentrations of lipophilic weak bases in upper small intestine was investigated with BioGIT by using albendazole free base [ABZ, pka 2.80 (Jung et al 1998), logP 3.46 (Rivera et al 2007)] as a model lipophilic weak base. There were three specific objectives of the present study:…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System

Kourentas

Vertzoni

Khadra

et al. 2016

Journal of Pharmaceutical Sciences

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This version is available at https://strathprints.strath.ac.uk/58946/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. AbstractAn in vitro biorelevant transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipidic self-emulsifying vehicles).The in vitro method was then used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately mimicked the average albendazole gastrointestinal transfer process and in vivo concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation seen initially in the duodenuum was greater in-vitro than in-vivo.Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole.3

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Absorption Studies of Albendazole and Some Physicochemical Properties of the Drug and Its Metabolite Albendazole Sulphoxide

Cited by 118 publications

References 13 publications

Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.

Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.

Improved Albendazole Dissolution Rate in Pluronic 188 Solid Dispersions

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System

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